Recovery of the biphasic hypoxic ventilatory response in neonatal rats after chronic hyperoxia

Newborn mammals exhibit biphasic hypoxic ventilatory responses (HVR) characterized by an initial increase in ventilation and a secondary ventilatory depression. The magnitude of the hypoxic ventilatory decline (HVD) in the late phase of the HVR normally decreases with age, but this occurs sooner in rats reared in 60% O₂. We investigated whether a lower level of hyperoxia (30% O₂) or a short period of recovery (1 or 3 d in 21% O₂) would affect the expression of this plasticity. Similar to 60% O₂, rat pups reared in 30% O₂ until 3-4 days of age exhibited a less biphasic HVR to 12% O₂. When pups reared in 60% O₂ were returned to normoxia, the magnitude of HVD increased such that pups expressed a biphasic HVR appropriate for their chronological age. Blocking synaptic input from the carotid bodies revealed that CNS hypoxia depressed ventilation less in hyperoxia-reared rats immediately following hyperoxia and after 1 d in normoxia despite recovery of the biphasic HVR. This suggests that recovery of the biphasic HVR occurs in pathways regulating HVD that depend on carotid body activity. The early, carotid body-mediated phase of the HVR was also blunted immediately and 1 d after the hyperoxia exposure, but not after 3 d of recovery. These data confirm that short exposures to mild-to-moderate hyperoxia elicit developmental plasticity in the HVR. However, reemergence of the biphasic HVR after return to normoxia argues against a heterokairic process for the premature transition from biphasic HVR to sustained HVR in hyperoxia-reared rat pups.